This invention relates to the field of tissue synthesis and in particular, to methods for the formation of biopolymer fibers.
The need to replace tissue lost to disease or injury or as a result of surgical intervention has been a long standing one. Although wound repair can occur in the absence of tissue replacement, such wound repair is often accompanied by severe scarring and loss of function. In those cases in which a patient suffers from a circulatory disorder or from diabetes, a dermal wound may fail to heal for months or years. This extended failure of wound healing often leads to infection and chronic discomfort. More seriously, under many circumstances severe tissue loss can be life threatening and replacement or surgical restoration becomes an absolute necessity.
One approach to accelerating the body""s self-healing process is to provide a scaffolding made of a biocompatible material populated with appropriate cells. A highly desirable type of scaffolding can be fabricated from a naturally occurring biopolymer fiber such as collagen fiber.
It has been traditionally difficult to spin collagen fibers which have dimensional and strength properties like those which occur in organisms in vivo. Fibers produced by methods which preserve the inherent biological information break easily when subjected to even small mechanical stress. It is therefore desirable in the art to provide a method and apparatus for manufacturing collagen fiber of multiple deniers under conditions which minimize stress on the fiber.
Because the collagen fiber is ultimately destined for implantation in a human body, it is desirable that it be free of contamination by extraneous matter and micro-organisms. Consequently, it is desirable in the art to provide a method and apparatus for manufacturing collagen fiber in which the resultant fiber is reasonably free of such contaminants.
The formation of a fiber in a manner that reduces the mechanical stress on the fiber is accomplished, in an apparatus embodying the invention, by providing a fiber-formation tube that defines a tube axis extending generally vertically from an upper end to a lower end and having an inner wall defining a bore within the fiber-formation tube.
At the upper end of the fiber-formation tube is a fluid inlet for establishing a flow of coagulation fluid in a coagulation zone of the bore. A spinneret is then coupled to the bore at a point downstream from the fluid inlet so as to introduce a biopolymer into the coagulation zone. When introduced to the coagulation zone in this manner, the biopolymer is immediately surrounded by coagulation fluid. At the same time, the flow of coagulation fluid keeps the biopolymer from contacting the inner wall of the bore and sweeps the biopolymer downstream as it coagulates.
At a selected distance downstream from the spinneret, the biopolymer stream is fully coagulated to form a biopolymer fiber. At this point, or alternatively, anywhere downstream from this point, a fluid outlet is provided to separate the coagulation fluid from the coagulated biopolymer fiber. In another embodiment, the fiber is collected and retained with the coagulation fluid.
In either of these embodiments, coagulation of the fiber can be followed by cross-linking of the fiber. This is achieved by adding chemical cross-linking agents to the coagulation fluid or to a fluid that replaces the coagulation fluid. Cross-linking agents known in the art include aldehydes such as glutaraldehyde and formaldehyde; sugars such as ribose and fructose; acrylamides such as N,Nxe2x80x2-methylenebisacrylamide;carbodiimides, such as 1-ethyl-3-(dimethyaminopropyl) carbodiimide; diones, such as 2,5-hexanedione; diimidates, such as dimethylsuberimidate; and iridoid derivatives such as genipin.
An apparatus embodying the invention can further minimize the mechanical stress experienced by the fiber as it coagulates by establishing a laminar flow of coagulation fluid within a laminar zone of the bore. As used herein, xe2x80x9claminar flowxe2x80x9d refers to uniform laminar flow in which the velocity profile of the flow is symmetric about the tube axis. The term xe2x80x9cnon-uniform flowxe2x80x9d refers to flow having an asymmetric velocity profile. This includes both laminar flow having an asymmetric velocity profile and non-laminar flow.
In this embodiment, the coagulation fluid inlet is coupled to an upstream end of the fiber-formation tube and disposed to create a laminar flow generally parallel to the tube axis. As a result of the laminar flow, no significant transverse forces disturb the coagulating fiber.
An advantage of an apparatus incorporating the invention is that because the fiber is relatively free of any mechanical stresses during its formation, very long and fine fibers approaching the dimensions and strengths of in vivo fibers can be readily produced.
Yet another advantage of an apparatus incorporating the invention is that because the fiber-formation tube is narrow, only a limited amount of coagulation fluid is needed. As a result, it is economically feasible to discard coagulation fluid after a single use and to use only fresh coagulation fluid during the fiber-formation process. This enables the resulting fiber to be more readily made aseptic and, therefore, more suitable for use in a patient.
The method of practicing the invention includes the steps of generating a laminar flow of coagulation fluid having an upstream direction and a downstream direction and introducing a biopolymer stream into the laminar flow. The coagulation fluid envelops the biopolymer stream and propels it in the downstream direction while coagulating it. In this way, a biopolymer fiber is formed. The biopolymer fiber may then be separated from the coagulation fluid if desired. In one embodiment, the separation is accomplished by providing a fluid diverter. In another embodiment, the separation is accomplished by surrounding the fiber with a dehydration fluid.